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Author Liu, Shan-Chi ♦ Lee, Hsiang-Ping ♦ Hung, Chun-Yin ♦ Tsai, Chun-Hao ♦ Li, Te-Mao ♦ Tang, Chih-Hsin
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ CARTILAGE ♦ DAMAGE ♦ DRUGS ♦ FIBROBLASTS ♦ IN VITRO ♦ IN VIVO ♦ INFLAMMATION ♦ LYMPHOKINES ♦ PATHOGENESIS ♦ PHOSPHOTRANSFERASES ♦ PLANT GROWTH ♦ RATS
Abstract Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator that is abundantly expressed in osteoarthritis (OA). Interleukin-1β (IL-1β) plays a pivotal role in OA pathogenesis. Berberine exhibits an anti-inflammatory effect, but the mechanisms by which it modulates CCN2-induced IL-1β expression in OA synovial fibroblasts (OASFs) remain unknown. We showed that CCN2-induced IL-1β expression is mediated by the activation of α{sub v}β{sub 3}/α{sub v}β{sub 5} integrin-dependent reactive oxygen species (ROS) generation, and subsequent activation of apoptosis signal-regulating kinase 1 (ASK1), p38/JNK, and nuclear factor-κB (NF-κB) signaling pathways. This IL-1β expression in OASFs is attenuated by N-acetylcysteine (NAC), inhibitors of ASK1, p38, or JNK, or treatment with berberine. Furthermore, berberine also reverses cartilage damage in an experimental model of collagenase-induced OA (CIOA). We observed that CCN2 increased IL-1β expression via α{sub v}β{sub 3}/α{sub v}β{sub 5} integrins, ROS, and ASK1, p38/JNK, and NF-κB signaling pathways. Berberine was found to inhibit these signaling components in OASFs in vitro and prevent cartilage degradation in vivo. We suggest a novel therapeutic strategy of using berberine for managing OA. - Highlights: • CCN2 induce IL-1β production via αvβ3/αvβ5 integrin, ROS, ASK1, p38/JNK, and NF-κB. • Berberine attenuates CCN2-induced IL-1β expression in vitro and in OA rat model. • Berberine as natural drug of choice for anti-inflammatory effect to ameliorates OA.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-11-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 289
Issue Number 1


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